SMAD6/MADH6; mothers against decapentaplegic homolog 6; mothers against DPP homolog 6; MAD homolog 6; SMAD family member 6; SMAD 6; smad6; hSMAD6 (SMAD6, MADH6)

Function

• antagonist of signaling by TGF-beta type 1 receptor superfamily members
• inhibits selectively BMP (bone morphogenetic proteins) signaling by competing with the co-SMAD SMAD4 for receptor-activated SMAD1
• inhibits phosphorylation of SMAD2 but perhaps not SMAD3
• SMAD6 is an inhibitory SMAD (I-SMAD) or antagonistic SMAD
• binds to regulatory elements in target promoter regions
• phosphorylated by BMP type 1 receptor kinase & by PRKX
• interacts with NEDD4L (putative)
• interacts with RNF111 & AXIN1
• interacts with TGF-beta type 1 receptor superfamily members, SMAD1, HOXC8 & HOXC9
• interacts with STAMBP & PRKX

Structure

• belongs to the dwarfin/SMAD family
• contains 1 MH1 (MAD homology 1) domain
• contains 1 MH2 (MAD homology 2) domain

Compartment

• nucleus

Alternative splicing

• named isoforms=3; A, B, D

Expression

• ubiquitous in various organs, with higher levels in lung
• isoform B is up-regulated in diseased heart tissue

More general terms

• SMAD protein
• phosphoprotein
• nuclear protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4091
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4091
• OMIM: https://mirror.omim.org/entry/602931
• UniProt: http://www.uniprot.org/uniprot/O43541.html